Wednesday, November 29, 2023

Novo Nordisk to Discontinue Levemir in 2024

Upgrade to Patent-Protected Tresiba — or else!

On Wednesday, November 8, 2023, Novo Nordisk announced that it would discontinue its long-acting insulin Levemir (insulin detemir injection) in the United States, citing manufacturing constraints, reduced patient access and available alternatives. The company's official statement (see said: 

"We will continue to provide Levemir FlexPen and Levemir vials to wholesalers while supplies last, up to the discontinuation dates, but supply disruptions should be expected."

It added further: "Levemir FlexPen, the injection pen version of insulin detemir, will likely face supply disruption starting in mid-January 2024, lasting up until the FlexPen's discontinuation on April 1. Levemir in vial form will no longer be available after Dec. 31, 2024." 

The company also warned of imminent supply chain issues. 

"Discontinuing Levemir was the result of thoughtful deliberation", according to the statement. 

That line of bullshit I've heard previously from Novo Nordisk.

What it "deliberated" was to ask whether can it deploy an old tactic of forced upgrades following discontinuation of a product? The answer to that may not be yes as of 2023. I recall when Novo Nordisk originally discontinued Novolin L(ente). The good news for me was that at the time, Lilly still made that product for about a year or two after Novo pulled the plug on it, so I just switched without issue until Lilly stopped making it. As of 2023, Lilly doesn't even have a proprietary basal insulin of its own, only a biosimilar of Lantus (Rezvoglar, known generically as insulin glargine-aglr) and a follow-on version of Lantus (branded Basaglar, which was approved when Lantus was still governed as a drug rather than a biologic, hence it was approved under a different FDA approval process).

For its part, Novo Nordisk introduced a newer, still patent-protected basal insulin branded as Tresiba (insulin degludec injection) in 2015 which has been its primary marketing focus on basal insulins, especially since Levemir lost all U.S. patent exclusivity in April 2021. Tresiba and the unbranded version have been in short supply for some time. Payers, on the other hand, were not willing to pay a premium price for Tresiba or even the unbranded version of it. Right now there are already several biosimilars of Sanofi's Lantus on the market, and at least five more are anticipated to be considered by FDA in 2024 and another from Meitheal Pharmaceuticals (assuming its biosimilar is FDA approved) a few years after. Once again, while Tresiba may be superior (it was only Novo Nordisk's second attempt at a "Lantus killer") as a basal insulin (flatter curve of action, longer-lasting in the bloodstream), but when rebates on insulin go away starting in 2024, the market dynamic could change for Novo Nordisk's newest Lantus killer.

The decision to pull the plug on Levemir was unexpected. Earlier this year, in March 2023, Novo Nordisk announced that effective beginning January 1, 2024, Levemir would be listed at $107.85 per vial (or $161.77 per FlexPen) which was 65% lower than that product had been priced at previously. However, recall that in September 2022, Novo Nordisk introduced two "unbranded" versions of Tresiba (U-100 and U-300 for the severely insulin-resistant Type 2 diabetes patient market, which I covered HERE) designed to bypass PBM list price inflation caused by ever-higher legally-exempted rebate kickbacks demanded by PBMs to secure formulary placement. 

When Lilly slashed its insulin list prices in March 2023, Novo Nordisk and Sanofi followed suit almost immediately (both were pretty much forced to do so; although they had likely been considering doing so anyway), and to pay for those cuts, they would simply disintermediate the Pharmacy Benefit Managers (PBMs) and voila: it costs the manufacturers almost NO money, and patients win.

Nevertheless, the discontinuation of older, patent-expired insulins is hardly a new development for Novo Nordisk (or Lilly, for that matter). The company has routinely operated from a mindset of forcing patients and their doctors to "upgrade" them to newer, more-expensive and still-patent protected insulin varieties because they were given no choice. 

But those all happened prior to the advent of biosimilar insulins.

Biosimilars opens the prospect that the innovator company may stop making a product, but copycat biosimilars could theoretically emerge selling a version of the same product made by a different company available. So far, that has not happened, but it remains a possibility on a patent-expired basal insulin such as Levemir.

diaTribe news reported (see 

"Levemir represents a sizable portion of the basal insulin market (it generated $649 million in revenue in 2022 alone)." With Levemir being taken off the market, theoretically the advent of FDA-approved biosimilar insulins which means that potentially, a biosimilar company could potentially step in to manufacture Levemir and then sell it, although perhaps not timely-enough to be available when Novo Nordisk's branded Levemir is no longer available on the U.S. market. Theoretically, however, one could emerge which is an interesting possibility.

In spite of their vastly lower prices, biosimilars have been very slow to take-off in the United States. As I have written in the past, in the U.S., costly but heavily-rebated products are much more likely to secure formulary placement. The artificially-inflated list prices are driven by legally-exempted rebate kickbacks paid to PBMs to secure formulary placement. But in 2022, the Federal Trade Commission (FTC) unanimously announced it would undertake a comprehensive 6(b) study of PBM business practices. The prospect of that, combined with the passage of the American Rescue Plan Act of 2021 which capped Medicaid rebates at 100% of the Average Manufacturer Price (AMP), may force biopharmaceutical companies to take further action to reduce prices. Companies with biopharmaceuticals with high list prices and significant rebates (e.g., older branded medicines such as insulin) may have been forced to pay Medicaid to cover those drugs. Let that sink in; companies would have to pay Medicaid instead of getting paid by Medicaid for having their medicine on the list of covered medications. The only remedy for such companies is to lower their prices drastically to avoid negative pricing consequences.

Anyway, no doubt Novo Nordisk in 2024 hopes to replicate its previous "upgrade because we're not making the older product you once relied upon anymore" has a number of unknowns this time around. 

For one thing, there is nothing stopping a biosimilar manufacturer stepping in to sell biosimilar versions of Levemir. Or, Lilly and/or Sanofi could potentially make ones, too. Either are now possibilities which simply did not exist until 2019.

Personally, I like the idea of biosimilars, although I'm not certain we'll see any for Levemir, although it remains a theoretical possibility. Also a possibility is that a big insulin-maker with a miniscule share of the basal insulin market such as Lilly might decide to make it (after all, $649 million in revenue in 2022 would be there for the taking if it could move quickly enough).  Levemir is viewed as an older, dying product and every one of the biosimilar companies to my knowledge plan on launching Lantus biosimilars in 2024, combined with Sanofi's branded and unbranded versions as well as 6 or 7 biosimilars does not make Novo Nordisk's Tresiba a guaranteed success story (why there are market shortages is a different question; as I understand it, Novo Nordisk does not manufacture that product in the U.S., rather it imports it from Denmark). Much depends on timing. The short notice Novo Nordisk is giving aim to make the prospect of copies more difficult.

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